23- Antibacterial Responses

Question 1

pathogenic mechanism of S. aureus?

Answer 1

alpha toxin which forms pores in cell membranes = causes cell lysis

enterotoxins like superantigens = contribute to toxic shock syndrome

Question 2

pathogenic mechanism of V. cholerae?

Answer 2

cholera toxin ribosylates Gs protein = increases cAMP levels in intestinal cells = severe diarrhoea with affected ionic balance

Question 3

pathogenic mechanism of M. tuberculosis?

Answer 3

inhibits phagosome-lysosome fusion , allows survival inside macrophages

chronic inflammation and granuloma formation contains bacteria and causes tissue damage

Question 4

pathogenic mechanism of N. meningitidis?

Answer 4

polysaccharide capsule protects against phagocytosis

LOS causes severe inflammatory response & septic shock

Question 5

key characteristics of an infection

Answer 5

entry, invasion and colonisation of tissue, evading immunity, tissue damage

Question 6

mechanical innate immunity barriers

Answer 6

flow of fluids and airflow
mucus
saliva
sperm
secretions like tears

Question 7

chemical component of innate immunity barriers

Answer 7

secretions have chemical components:
fatty acids, lysosomes, enzymes

low pH creates a harsh environment, harder for bacteria to develop and colonise

antimicrobial peptides like defensins - released into extrac. space, harmful to bacterial cells

Question 8

microbiological barriers of innate immunity

Answer 8

normal flora of the skin, GI tract, resp and urogenital tract, and eyes

protect us, prevent bacteria from establishing a niche, prevent unwanted immune responses

Question 9

main types of receptors expressed by macrophages for phagocytosis?

Answer 9

high levels of complement receptors - e.g. CR1, 3, 4
pattern recognition receptors - e.g. TLRs, NLRs
scavenger receptors
antibody-binding Fc receptors

Question 10

how do complement receptors on macrophages aid in phagocytosis?

Answer 10

detect bacteria tagged by complement molecules

enable more efficient internalization and phagocytosis of the microbe

Question 11

what happens when macrophages detect bacterial components through their TLRs?

Answer 11

e.g. PAMPs - detected through TLRs = macrophage becomes activated and produces cytokines

initiates an inflammatory response

Question 12

describe the two processes involving macrophage complement receptors and phagocytosis

Answer 12

1. complement tagging microbes for elimination - macrophages detected complement-tagged microbes via their CRs and engulf it
2. detect infection through PRRs, leads to cytokine production and initiating an inflammatory response

Question 13

what are Pattern Recognition Receptors (PRRs) - why are they important?

Answer 13

PRRs = diverse group of receptors that detect bacterial presence, key to the antibacterial response

e.g. membrane-bound, insoluble TLRs and NLRs
e.g. soluble receptors like complement components

Question 14

TLR4 - bacterial feature it detects?

Answer 14

LPS/ lipopolysaccharides (extrac. TLR)

Question 15

TLR2 -bacterial feature it detects?

Answer 15

peptidoglycans (extrac. TLR)

Question 16

TLR9 - bacterial feature it detects?

Answer 16

intracellular CPG bacterial DNA

Question 17

consequences of macrophages detecting PAMPs through TLRs?

Answer 17

1. phagocytosis of pathogen
2. production of inflammatory cytokines & chemokines = inflammatory response

Question 18

explain the process of phagocytosis when a macrophage detects PAMPs

Answer 18

PAMP binds to a PRR on a macrophage - activates a macrophage, increases its metabolic activity

macrophage ingests and degrades the microbe - releases chemokines, cytokines, NO & degradative enzymes to enhance its antimicrobial activity

Question 19

what initiates the process of inflammation?

Answer 19

resident tissue immune cells detecting infection

become activated and produce pro-inflammatory cytokines & chemokines - e.g. TNF-alpha, IL-6, IL-1

Question 20

how do cytokines and chemokines affect the endothelium during inflammation?

Answer 20

change characteristics of endothelium, allow circulating leukocytes to move to the site of infection/ damage

Question 21

order of recruited leukocytes during inflammation?

Answer 21

neutrophils - clear extrac. bacteria, have a potent antibacterial response

monocytes

specific lymphocytes

local cells like mast cells

Question 22

describe the antibacterial mechanisms of neutrophils (3)

Answer 22

1. phagocytosis and degranulation of granules
   - neutrophils phagocytose bacteria, antimicrobial proteins from degranulated granules kill bacteria
2. phagocytosis and oxidative killing of bacteria
   - production of ROS and NOS to kill bacteria
3. NETs killing bacteria
   - undergo NETosis to produce extrac. fibres of DNA, histones and antimicrobial proteins to trap & kill bacteria

Question 23

three main functions of antibodies?

Answer 23

neutralise bacterial toxins

trigger classical complement pathway – by binding of IgM to the bacterial cell surface

opsonisation – coating bacteria with antibody thereby aiding phagocytosis

Question 24

how do antibodies neutralise toxins?

Answer 24

antibodies block toxin by preventing it from binding to a receptor on a target cell

no toxin internalisation or disruption of cell function to cause damage/ cell death

Question 25

how are antibodies involved in opsonisation?

Answer 25

antibodies coat bacteria, then interact with Fc receptors on phagocytes = allows for more efficient phagocytosis

antibodies also aid complements (activate classical pathway) - C3b coats bacteria, recognised by macrophage CRs for efficient phagocytosis

Question 26

how do antibodies activate the complement cascade?

Answer 26

IgM/ IgG bound to bacterium surface antigen - C1q binds to immune complex = triggers classical pathway

bacterial surface becomes coated with C3B = efficient phagocytosis

Question 27

antibody class best at opsonisation

Answer 27

IgG 1 & 3

Question 28

antibody class best at neutralising toxins

Answer 28

IgA

Question 29

antibody class best at activating the complement system

Answer 29

IgM and IgG 1& 3